Depth profiling of mammalian cells by photoacoustic spectroscopy: localization of ligands.

Phase-resolved monitoring of photoacoustic signals can provide information about the depth profile of a sample. We describe an application of this principle to determine the depth profiles of ligands and antitumor agents in mammalian cells. Measurements of the in-phase and quadrature components of the photoacoustic spectra (which yield information from the surface and the interior, respectively) of a tumor cell line, AK-5, treated with the antitumor agent coralyne chloride have been made. They clearly show that the drug accumulates in the cell interior and is not seen on the cell surface, providing in situ evidence for the localization of this drug. Histochemical dyes which stain cells uniformly give identical in-phase and quadrature spectra; spectra of cells incubated with nuclear stains demonstrate a differential staining of the nucleus and the cytoplasm. These results demonstrate the usefulness of phase-resolved photoacoustic spectroscopy in monitoring differential interactions of drugs and other ligands with cells.